Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
Qi, Wei; Chan, HoMan; Teng, Lin; Li, Ling; Chuai, Shannon; Zhang, Ruipeng; Zeng, Jue; Li, Min; Fan, Hong; Lin, Ying
2012
发表期刊PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
卷号109期号:52页码:21360-21365
发表状态已发表
DOI10.1073/pnas.1210371110
摘要

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.

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收录类别SCI
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000313627700051
WOS关键词EMBRYONIC STEM-CELLS ; HISTONE H3 ; LYSINE 27 ; DEVELOPMENTAL REGULATORS ; SOMATIC MUTATIONS ; B-CELLS ; POLYCOMB ; GENE ; LYMPHOMA ; CANCER
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120271
专题个人在本单位外知识产出
共同第一作者Chan, HoMan
通讯作者Li, En
作者单位1.China Novartis Inst BioMed Res, Shanghai 201203, Peoples R China
2.Novartis Inst BioMed Res, Ctr Prote Chem, Cambridge, MA 02139 USA
推荐引用方式
GB/T 7714
Qi, Wei,Chan, HoMan,Teng, Lin,et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109(52):21360-21365.
APA Qi, Wei.,Chan, HoMan.,Teng, Lin.,Li, Ling.,Chuai, Shannon.,...&Li, En.(2012).Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,109(52),21360-21365.
MLA Qi, Wei,et al."Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.52(2012):21360-21365.
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